Bioinorganic hybrid bacteriophage for modulation of intestinal microbiota to remodel tumor-immune microenvironment against colorectal cancer
SCIENCE ADVANCES
Authors: Dong, Xue; Pan, Pei; Zheng, Di-Wei; Bao, Peng; Zeng, Xuan; Zhang, Xian-Zheng
Abstract
Mounting evidence suggests that the gut microbiota contribute to colorectal cancer (CRC) tumorigenesis, in which the symbiotic Fusobacterium nucleatum (Fn) selectively increases immunosuppressive myeloid-derived suppressor cells (MDSCs) to hamper the host's anticancer immune response. Here, a specifically Fn-binding M13 phage was screened by phage display technology. Then, silver nanoparticles (AgNP) were assembled electrostatically on its surface capsid protein (M13@Ag) to achieve specific clearance of Fn and remodel the tumor-immune microenvironment. Both in vitro and in vivo studies showed that of M13@Ag treatment could scavenge Fn in gut and lead to reduction in MDSC amplification in the tumor site. In addition, antigen-presenting cells (APCs) were activated by M13 phages to further awaken the host immune system for CRC suppression. M13@Ag combined with immune checkpoint inhibitors (alpha-PD1) or chemotherapeutics (FOLFIRI) significantly prolonged overall mouse survival in the orthotopic CRC model.
Non-lytic M13 phage-based highly sensitive impedimetric cytosensor for detection of coliforms
BIOSENSORS & BIOELECTRONICS
Authors: Sedki, Mohammed; Chen, Xingyu; Chen, Chuan; Ge, Xin; Mulchandani, Ashok
Abstract
A highly sensitive and selective non-lytic M13 phage-based electrochemical impedance spectroscopy (EIS) cytosensor for early detection of coliforms is introduced for the first time. Gold nanoparticles were electrochemically deposited on the surface of glassy carbon electrode, and the M13 phage particles were immobilized on them using 3-mercaptopropionic acid linker and zero-length crosslinking chemistry (EDC/NHS). Next, the sensor surface was blocked to avoid non-specific binding. The M13-EIS cytosensor was tested for detection of F+ pill Escherichia coli species, using XL1-Blue and K12 strains, as examples of coliforms. The selectivity against non-host strains was demonstrated using Pseudomonas Chlororaphis. The binding of E. coli to the M13 phage on the cytosensor surface increased the charge transfer resistance, enabling detection of conforms. The biosensor achieved a limit of detection (LOD) of 14 CFU/mL, the lowest reported to-date using EIS-phage sensors, and exhibited a high selectivity towards the tested coliforms. The SEM micrographs confirmed the successful capturing of E. coli on the M13-based EIS cytosensor. Moreover, the sensor showed almost the same sensitivity in the simulated river water samples as in phosphate buffer, reflecting its applicability to real samples. On the other hand, this sensor system exhibited high stability under harsh environmental conditions of pH (3.0-10.0) and temperature as high as 45 degrees C for up to two weeks. Overall, this sensor system has excellent potential for real field detection of fecal coliforms.